Ia molecules appear to function as restriction elements in histocompatibility restricted antigen-recognition by T cells and as the products of specific immune response genes. In order to ghain insight into the mechanisms through which Ia antigens express these functions, we have prepared a series of Ia mutants. To do this, we showed that mouse B lymphoma cell lines could act as antigen presenting cells (APC). B lymphoma-B cell hybridomas between the H-2d/d lymphoma line M12.4.1 and H-2a/d B cells were prepared and shown to have I-Aa determinedAPC functions. A pair of monoclonal antibodies directed at distinct determinants on the I-Aa Ia molecule were used to select mutants which expressed one but lacked the other determinant. These mutants lost the ability to present hen egg lysozyme but retained the ability to present a polymer of glutamic acid, alanine, or tyrosine to H-2a T cells. The structural basis of this change in presentation specificity is under study.